Epilepsy, characterized by recurring seizures, is one of the most prevalent neurological disorders in the U.S. Despite decades of research, new anticonvulsant drugs, and advances in surgical therapy, a large number of patients suffer from intractable epilepsy or the side effects of drugs or surgical treatment. Brain stimulation for epilepsy has shown promise but requires further research. The long-term goal of the investigators is to develop effective non-invasive and minimally invasive electrical stimulation therapies for intractable epilepsy. Non-invasive transcutaneous electrical stimulation (TcES) via unique concentric ring electrodes on the scalp surface is proposed as an innovative approach to seizure control. Noninvasive methods for stimulation-induced seizure control avoid complications associated with intracerebral implants. The objective of this R21 project is to investigate in laboratory rats anticonvulsant and safety of TcES via concentric ring electrodes on the scalp surface. Based on promising preliminary results, three hypotheses are behind this research: " Hypothesis 1: TcES via concentric ring electrodes on the scalp surface has anticonvulsant effects. " Hypothesis 2: {The suppression of pilocarpine (PILO)-induced status epilepticus (SE) by TcES via concentric ring electrodes reduces SE-provoked neuronal death.} " Hypothesis 3: Effective TcES parameters do not cause damage to rat scalp or brain tissue. To achieve the project objective and test the hypothesis, three specific aims are set: " Aim 1: Analyze the effects of TcES via concentric ring electrodes on electrographic activity, behavioral manifestations, severity, latency to onset, and threshold of pentylenetetrazole (PTZ)-induced seizures in rats. (test Hypothesis 1) " Aim 2: {Verify the suppression of PILO-induced SE by TcES via concentric ring electrodes through histopathological evaluation of neuronal integrity.} (test Hypothesis 2) " Aim 3: Assess potential tissue damage due to TcES via concentric ring electrodes through histomorphological analysis. The integrity of both scalp and brain tissue will be assessed. (test Hypothesis 3) As an initial phase of our research, this R21 project lays the foundation for future investigations of TcES in additional areas of importance. PUBLIC HEALTH RELEVANCE: If the proposed research is successful, in the future TcES may promise a viable non-invasive therapy for intractable epilepsy. A non-invasive therapeutic strategy for bedside and/or out-of-hospital intervention can significantly improve morbidity and mortality, as well as reduce risk and cost of treatment.